Epilepsy Research
Volume 30, Issue 3 , Pages 203-217, May 1998

Acute heat stress model of seizures in weanling rats: Influence of prototypic anti-seizure compounds

  • Gene C Palmer

      Affiliations

    • Astra Arcus USA, P.O. Box 20890, Rochester, NY 14602, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 716 2745575; fax: +1 716 2743910.
    • ,
  • Alfonso R Borrelli

      Affiliations

    • Astra Arcus USA, P.O. Box 20890, Rochester, NY 14602, USA
    • ,
  • Thomas J Hudzik

      Affiliations

    • Astra Arcus USA, P.O. Box 20890, Rochester, NY 14602, USA
    • ,
  • Sheldon Sparber

      Affiliations

    • University of Minnesota Medical School, Department of Pharmacology, 3249 Millard Hall, 435 Delaware Street SE, Minneapolis, MN 55455, USA

Received 17 June 1997; received in revised form 3 November 1997; accepted 24 December 1997.

Abstract 

The present study tested the therapeutic potential for prototype anti-epilepsy drugs using an animal model of infantile febrile seizures. The model consisted of immersion of weanling rats (21 days old) in a 45°C water bath for a maximum of 4 min (four exposures over a 2 week period) and observing for the progression to stage-5 seizures. All compounds were administered orally at the respective ED50 for prevention of seizures in the maximal electroshock (MES) test. Clonazepam effectively lowered the score for seizure grade, shortened the duration of seizures, as well as reduced the number of animals experiencing seizures during three of the four testing periods. MK801 reduced both the maximum seizure grade, and the number of animals experiencing seizures during sessions two and three. However, the dose of MK801 caused behavioral side effects. Valproate actively decreased seizure grade, while it modestly acted to attenuate seizure duration, extended the time to seizure onset, and reduced the number of animals experiencing seizures on testing day 1. Remacemide hydrochloride and phenobarbital were not effective. The method appears useful for evaluating the potential of agents to prevent acute febrile seizures.

Keywords:  Febrile seizures, Clonazepam, MK801, Remacemide, Valproate, Phenobarbital

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PII: S0920-1211(98)00002-3

Epilepsy Research
Volume 30, Issue 3 , Pages 203-217, May 1998

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